The MD-PhD Program at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences is designed to train physician-scientists. Our goal is to provide an outstanding cadre of investigators well-versed in both the conduct of basic and translational research and in the practice of medicine. We achieve this goal by providing a highly integrated approach to training, including a translational medical curriculum with the flexibility that dual degree students require. Medical training interfaces with five basic science PhD programs in Cell, Molecular, & Developmental Biology, Genetics, Immunology, Molecular Microbiology, and Neuroscience. Our program has continued to evolve during the past grant period years. We have enhanced trainee advising, created new MD-PhD Program courses and workshops that promote translational undertakings, provide strong student support, and improved program integration. Our June matriculation date and the ability for our students to explore research during their pre-clinical years of medical school enhance their informed choice of thesis lab and decrease time to degree. Our new medical curriculum allows students to complete a required clerkship prior to entering graduate school without delaying the start of research training. A second required four-week clerkship in Family Medicine is completed during graduate training, which allows students to stay firmly connected to clinical medicine and also facilitates flexibility in re- entry to medical training when the PhD is complete; students are able to maintain research momentum during that rotation by returning to the lab after hours and weekends. In addition to our Clinical Implications of Basic Research course, an annual retreat, and our career-oriented dinner program, we have added a series of skill- building workshops. These include preparation for the transition from graduate school to clinical medical training, mentoring for NIH application, a women physician-scientist group, and a workshop focused on choosing research-focused residencies. With a strong institutional commitment to the Program, we have expanded our enrollment through a Second Portal program for trainees already enrolled in medical school and increased the size of the incoming first year class to five trainees each year. Our Program has graduated 86 trainees since its inception and 40 are currently enrolled. We are requesting funding for 10 positions in this application.